title: Coronary blood flow in patients with stable coronary artery disease treated long term with folic acid and vitamin B12.
abstract: BACKGROUND
  Plasma concentration of total homocysteine is associated with risk of cardiovascular disease in epidemiological studies. We wanted to examine the effects of B-vitamin therapy, which may lower total homocysteine, on coronary flow and vascular function in patients with established coronary artery disease (CAD).
  
  
  METHODS
  Forty patients with stable CAD, mean (standard deviation) aged 57.8 (9.0) years, recruited into the Western Norway B-Vitamin Intervention Trial, were randomly assigned to daily oral treatment with 0.8 mg of folic acid and 0.4 mg of vitamin B12 or placebo, and 40 mg of vitamin B6 or placebo, using a 2 × 2 factorial design. At baseline, and after 9 and 24 months, coronary blood flow was assessed by coronary angiography and Doppler flow-wire measurements during intracoronary infusion of saline (basal), incremental doses of acetylcholine, adenosine, and nitroglycerin.
  
  
  RESULTS
  We found a significant increase in basal (P < 0.02) and adenosine-induced (P < 0.05) coronary blood flow in patients who received folic acid/vitamin B12 for 24 months, compared with placebo or vitamin B6 alone. Folic acid/vitamin B12 or vitamin B6 treatment did not change endothelial-dependent response after acetylcholine infusion or flow-dependent proximal dilatation in response to adenosine-induced maximal hyperemia (P ≥ 0.45).
  
  
  CONCLUSIONS
  Long-term treatment with a combination of folic acid and vitamin B12 increase basal and adenosine-induced maximal coronary blood flow. This may reflect improved microvascular function in patients with stable CAD.
authors.affiliation: Department of Heart Disease, Haukeland University Hospital, Bergen, Norway. oyvind.bleie@helse-bergen.no
authors.forename: Øyvind
authors.initials: Ø
authors.lastname: Bleie
authors.forename: Elin
authors.initials: E
authors.lastname: Strand
authors.forename: Per M
authors.initials: PM
authors.lastname: Ueland
authors.forename: Stein E
authors.initials: SE
authors.lastname: Vollset
authors.forename: Helga
authors.initials: H
authors.lastname: Refsum
authors.forename: Jannicke
authors.initials: J
authors.lastname: Igland
authors.forename: Jan E
authors.initials: JE
authors.lastname: Nordrehaug
authors.forename: Ottar K
authors.initials: OK
authors.lastname: Nygård
mesh_terms: D000109:Acetylcholine / Q000008:administration & dosage; D000241:Adenosine / Q000008:administration & dosage; D000368:Aged; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000503:physiopathology*; D003326:Coronary Circulation / Q000502:physiology*; D004311:Double-Blind Method; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage*; D005500:Follow-Up Studies; D006710:Homocysteine / Q000097:blood; D006801:Humans; D017078:Laser-Doppler Flowmetry; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D014805:Vitamin B 12 / Q000008:administration & dosage*; D025101:Vitamin B 6 / Q000008:administration & dosage
chemical_list: D006710:Homocysteine; D025101:Vitamin B 6; D005492:Folic Acid; D000241:Adenosine; D000109:Acetylcholine; D014805:Vitamin B 12